CN102936229A - 4-tertiary butyl-5-benzyl-2-acetyl aminothiazole with insecticidal activity and preparation method - Google Patents

4-tertiary butyl-5-benzyl-2-acetyl aminothiazole with insecticidal activity and preparation method Download PDF

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CN102936229A
CN102936229A CN2012105093268A CN201210509326A CN102936229A CN 102936229 A CN102936229 A CN 102936229A CN 2012105093268 A CN2012105093268 A CN 2012105093268A CN 201210509326 A CN201210509326 A CN 201210509326A CN 102936229 A CN102936229 A CN 102936229A
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tertiary butyl
salt
benzyl
chlorobenzyl
acylaminothiazole
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胡艾希
申坤
彭俊梅
欧晓明
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Hunan University
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Hunan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/44—Acylated amino or imino radicals
    • C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles

Abstract

The invention relates to 4-tertiary butyl-5-benzyl-2-acetyl aminothiazole as shown in a chemical structural formula I and salt thereof. in the formula I, Y1, Y2, Y3 and Y4 in the formula are selected from H, methyl, ethyl, hydroxy, methoxy, ethyoxyl, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoro methoxy; Z is selected from C1-C2 alkyls, C3-C4 linear alkyls or branched alkyls, C1-C2 alkyls containing chlorine, C3-C4 linear alkyls or branched alkyls containing chlorine, or aryl; and the salt is selected from hydrochloride, hydrobromide, sulfate, phosphate, mesylate, benzene sulfonate and tosilate. The 4-tertiary butyl-5-benzyl-2-aminothiazole is acylated to prepare 4-tertiary butyl-5-benzyl-2-acetyl aminothiazole. The invention also provides application of the 4-tertiary butyl-5-benzyl-2-acetyl aminothiazole with insecticidal activity and the salt thereof in preparation of insecticide.

Description

Have the 4-tertiary butyl of insecticidal activity-5-benzyl-2-acylaminothiazole and preparation method
Technical field
The present invention relates to preparation method and the application of new compound, specifically the synthetic application with as sterilant of the 4-tertiary butyl-5-benzyl-2-acylaminothiazole.
Background technology
Holla etc. [European Medical Chemistry, 2003,38:313-318] have described 2-virtue amino-4-(2,4-two chloro-5-fluorophenyls) preparation and the biological activity of thiazole compound; Chinese invention patent (ZL 200810032035.8) has been described the preparation of 4-acetylaminohydroxyphenylarsonic acid 3-(4-aryl thiazole-2-is amino) benzoic ether and as the application of desinsection and sterilant.
5-(4-the chlorophenylmethyl)-4-tertiary butyl-thiazolamine and hydrochloride, hydrobromate and nitrate [Acta Cryst. 2008, E64, o2350; Acta Cryst, 2010, E66, o735; Chinese invention patent, ZL 200910044019.5, and 2011.4.13 authorizes; ZL 201019060007.1,2011.6.15 authorize], 5-(2,4,5-trimethoxy phenmethyl)-the 4-tertiary butyl-thiazolamine [Acta Cryst. 2007, E63, o533], 5-(2-the chlorophenylmethyl)-4-tertiary butyl-thiazolamine hydrobromate [Acta Cryst, 2007, E63, o2534], 5-(2,4-dichlorobenzene methyl)-the 4-tertiary butyl-thiazolamine hydrobromate [Acta Cryst, 2010, E66, o568], 5-(3-trifluoromethyl the phenmethyl)-4-tertiary butyl-thiazolamine [Hunan University's journal (natural science edition), 2007, (10), 78] and 5,5 '-(1, the 3-xylylene) monocrystalline of two (the 4-tertiary butyl-thiazolamines), two hydrobromate monohydrates [Acta Cryst. 2007, E63, o2533] has been reported.5-(4-the chlorophenylmethyl)-4-tertiary butyl-thiazolamine hydrobromate is that important medicine intermediate: 5-(4-the chlorophenylmethyl)-4-tertiary butyl-thiazolamine hydrobromate is through neutralization, the compound that obtains with the aromatic aldehyde reaction has biological activity, in pharmacy, use [Hunan University's journal natural science edition as cox 2 inhibitor, 2009,36(2), 70-74; Chinese invention patent, CN 101492426].Chinese invention patent (CN1018445026, CN101781269) has been described the 5-(4-chlorophenylmethyl)-4-tertiary butyl thiazole and the 4-tertiary butyl-2-(nitrobenzyl imino-) preparation of thiazole:
Figure BDA0000251653661
Chinese invention patent (CN101277692A, 2008.10.01 is open) has been described the preparation of 5-benzyl-4-methyl/trifluoromethyl-2-virtue aminothiazole and hydrobromate thereof:
Figure BDA0000251653662
Figure BDA0000251653663
Chinese invention patent (CN102070556A, 2011.5.25 is open; CN102067845A, 2011.5.25 is open) preparation of 5-benzyl-4-alkyl-2-virtue aminothiazole hydrobromate described:
Figure BDA0000251653664
Summary of the invention
The object of the present invention is to provide the 4-tertiary butyl shown in the chemical structural formula I-5-benzyl-2-acylaminothiazole or its salt:
Figure BDA0000251653665
Y in the formula 1Be selected from: H, methyl, ethyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Y 2, Y 4Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Y 3Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Z is selected from: C 1~ C 2Alkyl, C 3~ C 4Straight or branched alkyl, chloride C 1~ C 2Alkyl, chloride C 3~ C 4The straight or branched alkyl or the aryl shown in the formula II:
Figure BDA0000251653666
R in the formula II 1, R 5Be selected from: H, methyl, ethyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; R 2, R 4Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; R 3Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Salt is selected from: hydrochloride, hydrobromate, vitriol, phosphoric acid salt, mesylate, benzene sulfonate, tosilate.
The object of the present invention is to provide the 4-tertiary butyl-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-kharophen thiazole hydrobromide salt.
The object of the present invention is to provide the 4-tertiary butyl-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 2-chlorobenzoyl is amino) thiazole hydrobromide salt.
The object of the present invention is to provide the 4-tertiary butyl-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 4-chlorobenzoyl is amino) thiazole hydrobromide salt
The object of the present invention is to provide the 4-tertiary butyl-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2,6-dichloro-benzoyl is amino) thiazole hydrobromide salt.
The object of the present invention is to provide the preparation method of the 4-tertiary butyl-5-benzyl-2-acylaminothiazole and salt thereof, it is characterized in that its preparation is undertaken by following reaction formula (1) or (2):
Y in the formula 1Be selected from: H, methyl, ethyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Y 2, Y 4Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Y 3Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Z is selected from: C 1~ C 2Alkyl, C 3~ C 4Straight or branched alkyl, chloride C 1~ C 2Alkyl, chloride C 3~ C 4The straight or branched alkyl or the aryl shown in the formula II.
The object of the present invention is to provide the 4-tertiary butyl-5-benzyl-2-acylaminothiazole and salt thereof in the preparation sterilant, to be applied.
The present invention compared with prior art has following advantage:
The present invention has prepared the 4-tertiary butyl-5-benzyl-2-acylaminothiazole and salt thereof first.The 4-tertiary butyl-5-benzyl-2-acylaminothiazole and salt thereof have insecticidal activity.
Embodiment
Following examples are intended to illustrate the present invention rather than limitation of the invention further.
Embodiment 1
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-kharophen thiazole and hydrobromate thereof
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 4.5 mL diacetyl oxides, stirring and dissolving, room temperature reaction, TLC monitoring reaction.After reaction is finished, under stirring, reaction solution is poured in the frozen water, separated out white solid, filter, drying gets the 4-tertiary butyl-5-(4-chlorobenzyl)-2-kharophen thiazole hydrobromide salt, yield 50.3 %, 220 ~ 221 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.34(s，9H，3×CH 3)，2.20(s，3H，CH 3)，4.20(s，2H，CH 2)，7.11(d，J?=?8.0?Hz，2H，C 6H 4?2,6-H)，7.25(d，J?=?8.0?Hz，2H，C 6H 4?3,5-H)，8.94(br，1H，NHCO）。
The 4-tertiary butyl-5-(4-chlorobenzyl)-2-kharophen thiazole hydrobromide salt makes the 4-tertiary butyl-5-(4-chlorobenzyl through ammonia treatment)-2-kharophen thiazole.
Embodiment 2
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-propionamido thiazole hydrobromide salt
Figure BDA00002516536610
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 4.5 mL propionic anhydrides, stirring and dissolving, room temperature reaction, TLC monitoring reaction.After reaction is finished, under stirring, reaction solution is poured in the frozen water, separated out white solid, filter, drying gets the 4-tertiary butyl-5-(4-chlorobenzyl)-2-propionamido thiazole hydrobromide salt, yield 69.2 %, 182 ~ 184 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.24(t，J?=?7.6?Hz，3H，CH 3)，1.34(s，9H，3×CH 3)，2.43(q，J?=?7.6?Hz，2H，CH 2CH 3)，4.20(s，2H，CH 2)，7.11(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.25(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，8.68(br，1H，NHCO）。
Embodiment 3
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-chloro acetylamino thiazole
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 20 mL tetrahydrofuran (THF)s, stirring and dissolving adds 0.4 mL pyridine, drip the chloroacetyl chloride that 0.4 mL is dissolved in 10 mL tetrahydrofuran (THF)s under the ice bath, 30 min drip off, and transfer room temperature reaction to, the TLC monitoring reaction.After reaction is finished, revolve the steaming solvent, add 30 mL water, dichloromethane extraction, the saturated sodium bicarbonate solution washing, anhydrous sodium sulfate drying is crossed post, gets the 4-tertiary butyl-5-(4-chlorobenzyl)-2-chloro acetylamino thiazole; Yield 60.2 %, 156 ~ 157 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.35(s，9H，3×CH 3)，4.21(s，2H，CH 2)，4.22(s，2H，ClCH 2)，7.11(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.26(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，9.43(br，1H，NHCO）。
Embodiment 4
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(2-chlorine propionamido) thiazole
Figure BDA00002516536612
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 20 mL tetrahydrofuran (THF)s, stirring and dissolving adds 0.4 mL pyridine, drip the chloroacetyl chloride that 0.6 mL is dissolved in 10 mL tetrahydrofuran (THF)s under the ice bath, 30 min drip off, and transfer room temperature reaction to, the TLC monitoring reaction.After reaction is finished, revolve the steaming solvent, add 30 mL water, dichloromethane extraction, the saturated sodium bicarbonate solution washing, anhydrous sodium sulfate drying is crossed post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2-chlorine propionamido) thiazole, yield 48.8 %, 135 ~ 137 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.36(s，9H，3×CH 3)，1.80(d，J?=?7.2?Hz，3H，CH 3)，4.21(s，2H，CH 2)，4.57(q，J?=?7.2?Hz，1H，CH)，7.11(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.26(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，9.48(br，1H，NHCO）。
Embodiment 5
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(3,5-dinitrobenzene formamido group) thiazole hydrobromide salt
Figure BDA00002516536613
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 3,5-dinitrobenzoic acid and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(3,5-dinitrobenzene formamido group) thiazole hydrobromide salt, yield 68.1 %, 93 ~ 95 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.47(s，9H，3×CH 3)，4.20(s，2H，CH 2)，7.16(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.31(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，9.15(d，J?=?2.0?Hz，1H，C 6H 3?4-H)，9.31(d，J?=?2.0?Hz，2H，C 6H 3?2,6-H）。
Embodiment 6
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(4-nitrobenzoyl amido) thiazole hydrobromide salt
Figure BDA00002516536614
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 4-nitrobenzoic acids and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, the TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(4-nitrobenzoyl amido) thiazole hydrobromide salt, yield 65.0 %, 184 ~ 185 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.37(s，9H，3×CH 3)，4.24(s，2H，CH 2)，7.15(d，J?=?8.4?Hz，2H，C 6H 4Cl?2,6-H)，7.28(d，J?=?8.4?Hz，2H，C 6H 4Cl?3,5-H)，8.13(d，J?=?8.8?Hz，2H，C 6H 4NO 2?2,6-H)，8.34(d，J?=?8.8?Hz，2H，C 6H 4NO 2?3,5-H)，9.75(br，1H，NHCO)。
Embodiment 7
The 4-tertiary butyl-5-(4-chlorobenzyl)-and 2-[2-(trifluoromethyl) benzamido] preparation of thiazole hydrobromide salt
Figure BDA00002516536615
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 2-trifluoromethylbenzoic acids and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, the TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-[2-(trifluoromethyl) benzamido] thiazole hydrobromide salt, yield 73.2 %, 125 ~ 127 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.34(s，9H，3×CH 3)，4.23(s，2H，CH 2)，7.16(d，J?=?8.4?Hz，2H，C 6H 4Cl?2,6-H)，7.28(d，J?=?8.4?Hz，2H，C 6H 4Cl?3,5-H)，7.63～7.64(m，3H，C 6H 4CF 3?3,4,5-H)，7.77～7.79(m，1H，C 6H 4CF 3?6-H)，8.91(br，1H，NHCO）。
Embodiment 8
The 4-tertiary butyl-5-(4-chlorobenzyl)-and 2-[3,5-two (trifluoromethyl) benzamido] preparation of thiazole hydrobromide salt
Figure BDA00002516536616
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 3,5-two trifluoromethylbenzoic acids and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-[3,5-two (trifluoromethyl) benzamido] thiazole hydrobromide salt, yield 80.3 %, 58 ~ 61 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.39(s，9H，3×CH 3)，4.22(s，2H，CH 2)，7.15(d，J?=?8.0?Hz，2H，C 6H 4?2,6-H)，7.29(d，J?=?8.0?Hz，2H，C 6H 4?3,5-H)，8.05(s，1H，C 6H 3?4-H)，8.47(s，2H，C 6H 3?2,6-H)，9.76(br，1H，NHCO）。
Embodiment 9
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(2-methyl-3-nitro benzamido) thiazole hydrobromide salt
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 2-nitro-3-tolyl acids and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, the TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2-methyl-3-nitro benzamido) thiazole hydrobromide salt, yield 67.0 %, 157 ~ 158 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.37(s，9H，3×CH 3)，2.59(s，3H，CH 3)，4.25(s，2H，CH 2)，7.16(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.29(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，7.45(t，J?=?8.0?Hz，1H，C 6H 3?5-H)，7.72?(d，J?=?8.0?Hz，1H，C 6H 3?6-H)，7.93?(d，J?=?8.0?Hz，1H，C 6H 3?4-H)，9.06(br，1H，NHCO）。
Embodiment 10
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(2,6-difluorobenzene formamido group) thiazole hydrobromide salt
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 2,6-difluoro-benzoic acid and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2,6-difluorobenzene formamido group) thiazole hydrobromide salt, yield 75.7 %, 130 ~ 132 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.35(s，9H，3×CH 3)，4.24(s，2H，CH 2)，7.02～7.03(m，2H，C 6H 3?3,5-H)，7.15(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.28(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，7.43～7.51(m，1H，C 6H 3?4-H)，9.22(br，1H，NHCO）。
Embodiment 11
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(2-methoxybenzoyl amino) thiazole hydrobromide salt
Figure BDA00002516536619
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol O-Anisic Acids and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, the TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 2-methoxybenzoyl is amino) thiazole hydrobromide salt, yield 56.3 %, 142 ~ 143 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.38(s，9H，3×CH 3)，4.10(s，3H，OCH 3)，4.23(s，2H，CH 2)，7.05(d，J?=?8.0?Hz，1H，CH 3OC 6H 4?3-H)，7.10～7.14(m，3H，C 6H 4Cl?2,6-H，CH 3OC 6H 4?5-H)，7.26(d，J?=?8.4?Hz，2H，C 6H 4Cl?3,5-H)，7.10～7.56(m，1H，CH 3OC 6H 4?4-H)，8.25(dd，J?=?8.0?Hz，J?=?2.0?Hz，1H，CH 3OC 6H 4?6-H)，10.82(br，1H，NHCO）。
Embodiment 12
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(2-chlorobenzoyl amino) thiazole and hydrobromate thereof
Figure BDA00002516536620
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 2-chloro-benzoic acids and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, the TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 2-chlorobenzoyl is amino) thiazole hydrobromide salt, yield 60.7 %, 105 ~ 107 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.34(s，9H，3×CH 3)，4.24(s，2H，CH 2)，7.15(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.27(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，7.35～7.48?(m，3H，C 6H 4?4,5,6-H)，7.79?(d，J?=?8.8?Hz，1H，C 6H 4?3-H)，9.47(br，1H，NHCO）。
The 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2-chlorobenzoyl amino) thiazole hydrobromide salt processes through sodium carbonate solution and makes the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 2-chlorobenzoyl is amino) thiazole.
Embodiment 13
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(4-chlorobenzoyl amino) thiazole and hydrobromate thereof
Figure BDA00002516536621
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 4-chloro-benzoic acids and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, the TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 4-chlorobenzoyl is amino) thiazole hydrobromide salt, yield 79.5 %, 115 ~ 117 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.36(s，9H，3×CH 3)，4.24(s，2H，CH 2)，7.14(d，J?=?8.0?Hz，2H，C 6H 4?2,6-H)，7.27(d，J?=?8.0?Hz，2H，C 6H 4?3,5-H)，7.48(d，J?=?8.8?Hz，2H，COC 6H 4?3,5-H)，7.88(d，J?=?8.8?Hz，2H，COC 6H 4?2,6-H)，9.49(br，1H，NHCO）。
The 4-tertiary butyl-5-(4-chlorobenzyl)-2-(4-chlorobenzoyl amino) thiazole hydrobromide salt processes through sodium carbonate solution and makes the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 4-chlorobenzoyl is amino) thiazole.
Embodiment 14
The 4-tertiary butyl-5-(4-chlorobenzyl)-preparation of 2-(2,6-dichloro-benzoyl amino) thiazole and hydrobromate thereof
Figure BDA00002516536622
1.2 the mmol 4-tertiary butyl-5-(4-chlorobenzyl)-thiazolamine hydrobromate, 1.6 mmol 2,6-dichlorobenzoic acid and 40 mL methylene dichloride, stirring at room, add 0.15 mmol DMAP, stirring reaction 0.5 h, add 1.6 mmol N, N '-dicyclohexylcarbodiimide, TLC monitoring reaction.After reaction is finished, remove by filter the part dicyclohexylurea (DCU), cross post, get the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2,6-dichloro-benzoyl is amino) thiazole hydrobromide salt, yield 71.2 %, 173 ~ 176 ℃ of m.p.. 1H?NMR(CDCl 3，400MHz)，δ：1.33(s，9H，3×CH 3)，4.23(s，2H，CH 2)，7.16(d，J?=?8.4?Hz，2H，C 6H 4?2,6-H)，7.29(d，J?=?8.4?Hz，2H，C 6H 4?3,5-H)，7.32～7.37?(m，3H，C 6H 3)，9.13(br，1H，NHCO）。
The 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2,6-dichloro-benzoyl amino) thiazole hydrobromide salt processes through sodium carbonate solution and makes the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2,6-dichloro-benzoyl is amino) thiazole.
Embodiment 15
The 4-tertiary butyl-5-benzyl-2-acylaminothiazole is measured black bean aphid and two-spotted spider mite cytotoxicity
1 for the examination target
Black bean aphid (Aphis fabae) is indoor with broad bean seedling raising sensitive strain for many years, if test is 3 age in days aphids with worm; Two-spotted spider mite (Tetranychus urticae) is indoor with broad bean seedling raising sensitive strain for many years.Test is healthy one-tenth mite with worm.
2 culture condition
Culture condition for target after examination target and the test is 25 ± 5 ℃ of temperature, relative humidity 65 ± 5%, periodicity of illumination 12/12h(L/D).
3 test medicines (former medicine): the 4-tertiary butyl-5-benzyl-2-acylaminothiazole and salt thereof.
4 medicaments are prepared former medicine: take by weighing aequum with ten thousand/electronic balance; Solvent: DMF (DMF), 0.2%; Emulsifying agent: Tween 80,0.2%; Add clear water and be diluted to desired concn.
5 test methods are with reference to " pesticide bioactivity is estimated SOP ".
The general sieve of black bean aphid adopts pickling process.If will cut with the broad bean seedling of 3 age in days broad bean aphids, dipping took out in 10 seconds afterwards in the liquid for preparing, and was inserted on the sponge that suctions water, covered the lampshade that starts, and every processing repeats for 2 times.Be disposed, be put into the observation indoor cultivation, regularly observe, check behind the 72h and the record death condition, calculate mortality ratio.
Two-spotted spider mite is adopted pickling process.To cut with the broad bean seedling of red spider, and soak taking-up in 10 seconds in the liquid for preparing, and suck unnecessary liquid around plant and the mite body with filter paper, and be inserted on the beaker that dress water sealed, every processing repeats for 2 times.Be disposed, be put into the observation indoor cultivation, regularly observe, check behind the 72h and the record death condition, calculate mortality ratio.
6 cytotoxicities
The cytotoxicity of preferred compound: when effective constituent concentration is 500mg/L, behind the processing 72h, the 4-tertiary butyl-5-(4-chlorobenzyl)-2-kharophen thiazole hydrobromide salt pair black bean aphid mortality ratio is 52.70%.When effective constituent concentration is 500mg/L, after processing 72h, the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2-chlorobenzoyl amino) thiazole hydrobromide salt, the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 4-chlorobenzoyl is amino) thiazole hydrobromide salt and the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2,6-dichloro-benzoyl is amino) thiazole hydrobromide salt pair two-spotted spider mite mortality ratio is respectively 78.87%, 50.73% and 77.23%.The 4-tertiary butyl-5-benzyl-2-acylaminothiazole and salt thereof have good insecticidal activity, can be used as the preparation sterilant and use in agricultural.

Claims (7)

1. the tertiary butyl of the 4-shown in the chemical structural formula I-5-benzyl-2-acylaminothiazole or its salt:
Figure FDA0000251653651
Y in the formula 1Be selected from: H, methyl, ethyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Y 2, Y 4Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Y 3Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Z is selected from: C 1~ C 2Alkyl, C 3~ C 4Straight or branched alkyl, chloride C 1~ C 2Alkyl, chloride C 3~ C 4The straight or branched alkyl or the aryl shown in the formula II:
Figure FDA0000251653652
R in the formula II 1, R 5Be selected from: H, methyl, ethyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; R 2, R 4Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; R 3Be selected from: H, methyl, ethyl, hydroxyl, methoxyl group, oxyethyl group, fluorine, chlorine, bromine, nitro, trifluoromethyl or trifluoromethoxy; Salt is selected from: hydrochloride, hydrobromate, vitriol, phosphoric acid salt, mesylate, benzene sulfonate, tosilate.
2. the described 4-tertiary butyl of claim 1-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-kharophen thiazole hydrobromide salt.
3. the described 4-tertiary butyl of claim 1-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 2-chlorobenzoyl is amino) thiazole hydrobromide salt.
Figure FDA0000251653654
4. the described 4-tertiary butyl of claim 1-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(the 4-chlorobenzoyl is amino) thiazole hydrobromide salt.
Figure FDA0000251653655
5. the described 4-tertiary butyl of claim 1-5-benzyl-2-acylaminothiazole salt is the 4-tertiary butyl-5-(4-chlorobenzyl)-2-(2,6-dichloro-benzoyl is amino) thiazole hydrobromide salt.
Figure FDA0000251653656
6. the preparation method of each described 4-tertiary butyl-5-benzyl-2-acylaminothiazole or its salt in the claim 1 ~ 5 is characterized in that the 4-tertiary butyl-5-benzyl-thiazolamine or its salt prepare the 4-tertiary butyl-5-benzyl-2-acylaminothiazole or its salt through acidylate; Preparation is undertaken by following reaction formula (1) or (2):
Figure FDA0000251653657
Y in the formula 1, Y 2, Y 3, Y 4, Z definition as claimed in claim 1.
7. each described 4-tertiary butyl-5-benzyl-2-acylaminothiazole or its salt application in the preparation sterilant in the claim 1 ~ 5.
CN2012105093268A 2012-12-03 2012-12-03 4-tertiary butyl-5-benzyl-2-acetyl aminothiazole with insecticidal activity and preparation method Pending CN102936229A (en)

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